OBJECTIVE:
To analyze the prognostic value of cardiomegaly, pulmonary congestion and cardiothoracic
ratio as indicators of death and survival in children with idiopathic dilated
cardiomyopathy (IDCM).METHODS: We carried out a retrospective review of 152 patients with idiopathic
dilated cardiomyopathy diagnosed between September 1979 and March 2003. In the
first 72 months, 722 exams were performed (100 in the first 15 days). Statistical
analysis: chi-square, Student's t test, ANOVA and Kaplan-Meier curves.
Alpha = 0.05; beta = 0.80.RESULTS: The mean age at presentation was 2.2±3.2 years. Idiopathic
dilated cardiomyopathy incidence was higher in children younger than 2 years
(76.3% - 95% CI = 68.7% to 82.8%) (p < 0.0001). Sex (p = 0.07) and color
(p = 0.11) were not significant and mortality was not influenced by age (p =
0.73), sex (p = 0.78) or color (p = 0.20). Most patients were severely ill (84.2%
- 95% CI = 77.4% to 89.6%; functional class III and IV; p < 0.0001). All
43 deaths occurred in this group (p = 0.0008). Cardiomegaly at presentation
was observed in 94.1% (95% CI = 89.1% to 97.2%) (p < 0.0001), and pulmonary
congestion in 75.6% (95% CI = 68.0% to 82.2%) (p < 0.0001). Pulmonary congestion
and cardiomegaly were more frequent in functional class III/IV patients (RC
= 8.03 - 95% CI = 2.85% to 23.1%) (p < 0.0001). Pulmonary congestion was
a marker of death (RC = 3.16 - 95% CI = 1.06% to 10.07) (p = 0.0222), but not
cardiomegaly (p = 0.1185). Survival was influenced by both cardiomegaly (p =
0.0189) and pulmonary congestion (p = 0.0050). Mean and maximum cardiothoracic
ratio were higher in the death group (0.749±0.053 vs. 0.662±0.080)
(p < 0.0001) and (0.716±0.059 vs. 0.620±0.085) (p < 0.0001).
ANOVA revealed a progressive decrease in cardiothoracic ratio in the survival
group (p < 0.0001).CONCLUSION: In children with idiopathic dilated cardiomyopathy, the presence
of pulmonary congestion at presentation and increased cardiothoracic ratio are
associated with poor survival.

Key words:
Idiopathic dilated cardiomyopathy, child, radiology.

Introduction

Heart failure (HF)
may be defined as a clinical syndrome in which the heart pump function is impaired,
not supplying the oxygenated blood necessary for normal tissue metabolism, growth
and development.1

Ventricular dysfunction
may be caused by an increase in afterload (severe aortic stenosis or chronic
hypertension), by an increase in preload (mitral regurgitation or left-right
shunt) or by intrinsic lesion to the heart muscle (myocarditis or dilated cardiomyopathy).2

According to the
World Health Organization, dilated cardiomyopathy is characterized by dilatation
and impaired contraction of the left ventricle or both ventricles.3
It may be idiopathic, familial/genetic, associated or not with inborn errors
of metabolism, viral and/or immune, alcoholic/toxic, or associated with recognized
cardiovascular disease in which the degree of myocardial dysfunction is not
explained by the abnormal loading conditions or the extent of ischemic damage.
Histology is nonspecific. Presentation is usually with heart failure, which
is often progressive. Arrhythmias, thromboembolism, and sudden death are common
and may occur at any stage.4-6

Idiopathic dilated
cardiomyopathy (IDCM) in pediatric patients is responsible for a large number
of emergency treatments and hospitalizations due to heart failure not associated
with congenital heart diseases, accounting for up to 29% of emergency treatments
of children aged less than two years.7 It has a high mortality rate,
with reported rates of 16%8 at 10 years, up to 49%,9 66%10
and even 80%,11 at five years. In patients who do not show a good
response to clinical treatment, heart transplant is the treatment of choice;
world experience presents an actuarial survival curve of 75 to 80% at one year
and of 60 to 75% at 5 years.12-14

IDCM is characterized
by HF associated with cardiomegaly and pulmonary congestion on chest X-ray and/or
left ventricle dilatation with reduced contractility on echocardiogram.

A radiological
examination of the study population was made in order to determine the importance
of chest X-ray as a prognostic factor for death in IDCM. The presence of cardiomegaly
and pulmonary congestion was assessed, and the cardiothoracic ratio was used
as prognostic factor and as survival marker.

Patients and
methods

A retrospective
study based on the data from Instituto Nacional de Cardiologia Laranjeiras
(National Institute of Cardiology - Laranjeiras) was carried out for later analysis
of the medical charts of 165 consecutive patients with IDCM diagnosed between
September 1979 and March 2003, with an age range from 1 to 15.6 years. Chest
X-ray of 152 (92.1%) out of 165 patients were retrieved and analyzed. The inclusion
criteria were presence of HF (dyspnea, dry cough, râles, tachycardia,
S3 rhythm, sweating and hepatomegaly), associated with the presence of cardiomegaly
on chest X-ray and/or left ventricle dilatation with reduced contractility on
echocardiogram. Patients with clinical diagnosis of myocarditis were not excluded
from the study. The clinical criteria suggestive of myocarditis were: fever;
chest pain; electrocardiogram (ECG) with low QRS voltages or conduction and
heart rhythm defects and elevated creatinine phosphokinase (CK) and its myocardial
fraction (CKmb)7. Patients with the following conditions were excluded
from the study: congenital heart diseases, anomalous coronary arteries, Kawasaki
disease, ventricular arrhythmogenic cardiomyopathy, ischemic damage due to neonatal
asphyxia or after cardiorespiratory resuscitation, use of cancer drugs, primary
arrhythmias, rheumatic valvular disease, neuromuscular diseases, arterial hypertension,
septicemia, HIV infection, Chagas disease and diphtheria.

The following variables
were analyzed:

Age at presentation
and range (before the age of two years vs after the age of two years), gender
and color. The patients were classified at presentation according to the New
York Heart Association (NYHA) functional classes (FC): FC I - without restrictions
on age-appropriate activities; FC II - comfortable at rest, however age-appropriate
activities result in symptoms of HF; FC III - comfortable at rest, however mild
physical activity results in symptoms of HF, and FC IV - symptoms of HF even
at rest, any physical activity increases discomfort.15

Initial and follow-up
chest X-ray : cardiothoracic ratio (CTR) and presence or absence of cardiomegaly
and pulmonary congestion were assessed on first chest X-ray. Cardiomegaly was
considered to be present when CTR was greater than 0.55 in the first year of
life and greater than 0.50 after the first year of life.16 Initial chest X-ray
was carried out in the first 15 days of follow-up on 100/67 patients (x = 1.49).
The highest CTR values (maximum CTR) presented by each patient were recorded.
A total of 773 chest X-rays, either posteroanterior (PA) or anteroposterior
(AP), depending on patient age (x = 5.09/patient), were performed, corresponding
to 172 months of radiological follow-up, 722 (x = 4.75/patient) patients in
the first 72 months of follow-up. The chest X-ray was assessed by two researchers
on different occasions, and the mean CTR was calculated for each X-ray. The
concordance between CTR values was 92.6%. The presence or absence of pulmonary
congestion was also analyzed by two researchers on different occasions, and
if they disagreed about the results, it was reassessed by a third researcher.

Classic drug therapy
for heart failure, consisting of oral digoxin, furosemide, spironolactone, captopril
and acetylsalicylic acid (ASA) was utilized for the prevention of thromboembolic
events. The analysis of the effect of treatment on patient outcome was not within
the scope of this study.

The statistical
analysis was made using Epi Info 6.04 of CDC (Centers for Disease Control
& Prevention) and Statistica 6.0 (Statsoft Inc.).

Dichotomous data
were assessed by the chi-square test (c2),
and when appropriate, the odds ratio (OR) and a 95%CI were used.

Continuous dependent
time variables were assessed by repeated measure analysis of variance for unbalanced
data, being grouped according to the type of outcome (survivor vs nonsurvivor)
and according to time to outcome.

Survival analysis
was made using Kaplan-Meier method.

An alpha value
of 0.05 and a beta value of 0.80 were used.

Ethical aspects

The study was
approved by the Research Ethics Committee of Instituto Nacional de Cardiologia
Laranjeiras and of Universidade do Estado do Rio de Janeiro.

Results

General aspects

Mean age at presentation
was 26.4±39.5 months (median = 8.40 months - 0 to 188 months) or 2.2±3.2
years (median = 0.69 year - 0 to 15.4 years). Mean follow-up period was 3.56
years (median = 2.23 years - 0 to 15.94 years). At the end of the study, 72
(47.3%) patients were followed up as outpatients, 10 (6.6%) were discharged
from hospital, 43 (28.3%) died and 27 (17.8%) were lost to follow-up. The mean
follow-up period in the latter group was 2.47 (0.1 to 7.89) years.

Cardiomegaly was
found in 94.1% (143) of the cases (p < 0.0001) (95%CI = 89.1% to 97.2%).
Pulmonary congestion was diagnosed in 75.6% (115) of the patients (p < 0.0001)
(95%CI = 68% to 82.2%), being more frequent in FC III and IV (82.8%) than in
FC I and II (37.5%) (p < 0.0001) (OR = 8.03 - 95% CI = 2.85% to 23.1%).

With regard to
cardiomegaly, no difference was noted between its incidence in the survivor
and nonsurvivor groups (p = 0.1185). Pulmonary congestion was a prognostic factor
for death (p = 0.0222) (OR = 3.16 - 95% CI = 1.06% to 10.07) (Table
1).

Survival curve
in the presence of cardiomegaly and pulmonary congestion at presentation

As to the finding
of cardiomegaly on chest X-ray, a clear difference in survival rates was observed
(p = 0.0189), indicating a worse prognosis in the presence of this finding (Figure
1). The same occurred in the presence of pulmonary congestion (p = 0.0050)
(Figure 2).

Cardiothoracic
ratio (CTR)

Maximum CTR observed
throughout the follow-up period showed significant difference between the groups.
The mean in the nonsurvivor group was 0.749±0.053 while in the survivor
group it was 0.662±0.080 (p < 0.0001) (Figure 3).

CTR was evaluated
at diagnosis and at 1, 3, 6, 12, 18, 24, 36, 48, 60 and 72 months. Mean CTR
was 0.620±0.085 in the survivor group and 0.716±0.059 in the nonsurvivor
group, showing statistical significance (p < 0.0001) (Figure
4). Follow-up CTR was different between the survivor and nonsurvivor groups
with a gradual decrease in the survivor group (p < 0.0001). Figure 5 shows
the follow-up of CTR in the first 72 months between both groups and the respective
95% confidence intervals, with a clear distinction between the groups after
three months.

Discussion

The sample described
in the present study is the most comprehensive one ever reported in the literature,
with the longest observation of childhood idiopathic dilated cardiomyopathy,
which reduces the possibility of sampling biases.

Mean age at presentation
was 2.2 years, 17 similar to most cases reported in the literature9,10,18-20;
however, some authors found higher means.8,11, 21,22 The onset of
the disease was found to preferably occur before the age of two years (76.3%),
in comparison with the group >2 years.17 Literature data
are controversial.18,19, 23,24 It may be inferred that the preference
of the disease for this age group (less than two years old) is due to the higher
incidence of viral infections in these patients.

Age at diagnosis
did not influence mortality,17 similarly to what was found in the
literature;25-27 however Arola et al.9 observed a higher
mortality rate among infants younger than one year old who suffer from endocardial
fibroelastosis and among male adolescents in the Finnish population, but other
authors found a higher mortality in patients older than two years.18,23,28

No difference was
observed as to the incidence of the disease with regard to gender,17
which is in agreement with the available literature.7-11,23,27,29-31
Gender did not show to have any influence on mortality in this study,17
which is in line with the findings of other authors.11,19,27 Despite
extensive search, we have not found other studies on the incidence and prognosis
of the disease with regard to ethnicity.

At initial diagnosis,
most patients (84.2%) were considered to have the severe form of the disease
(FC III and IV), 43 deaths occurring in this group of patients. In the study
conducted in Poland,22 no difference was noted as to the distribution
of disease severity and as to FC between the survivor and nonsurvivor groups.
Silva et al.29 showed predominance of less severe cases (FC I and
II), but they do not mention anything about the influence of FC on mortality.
Patients whose disease is classified as FC III and IV right at the beginning
and who do not respond to clinical treatment are more likely to die.

The methodology
used for analyzing the chest X-ray may result in an inherent interpretation
bias, but we believe that this bias could have been reduced by having two researchers
analyze the exams on different occasions, and by reaching a concordance of 92.6%.

Initial chest X-ray
revealed that cardiomegaly was present in most patients, thus showing that this
condition is a characteristic of the disease; however, pulmonary congestion
was characteristic of more severe cases (FC III and IV). Death could not be
predicted by the presence of cardiomegaly, but the presence of pulmonary congestion
on initial chest X-ray was a prognostic factor for death (p = 0.0222) (OR =
3.16). The analysis of the survival curve showed that the presence of cardiomegaly
influenced survival time, but the presence of pulmonary congestion is detrimental
to survival, and in its absence, after one year of follow-up, no patient died.

In the literature,
the incidence of cardiomegaly has been reported to be between 75.0% and 100%,29,32
depending on the severity of the studied patients; no association between
cardiomegaly and death was reported. Pulmonary congestion was described by Arola
et al.10 in 78.0% of patients, being a predictor of poorer outcome
(p = 0.06). Pulmonary congestion reveals left ventricle diastolic dysfunction
in which the final diastolic pressure of the left ventricle increases, being
aggravated by mitral regurgitation often found in IDCM, both of which elevate
the pressure inside the left atrium and pulmonary veins, causing pulmonary edema
into the alveoli, and different degrees of dyspnea.

Maximum CTR obtained
during follow-up was significantly lower in the survivor group than in the nonsurvivor
group; however, values overlapped, making the distinction between these groups
difficult. An identical finding was reported for mean CTR, which was lower in
the survivor group in comparison to the nonsurvivor group, with overlapping
values between groups, which did not allow us to determine the thresholds for
each type of outcome.

The literature
shows a distinct approach to the measurement of CTR, taking into account the
initial and follow-up CTR and its influence on death. Initial CTR was described
to be 0.600±0.080 and 0.660±0.058,19,23 with no difference
as to death; however, only one study revealed some difference between groups
(survivor = 0.571±0.061 vs nonsurvivor 0.651±0.068, p < 0.0001)
.11 Follow-up CTR was a prognostic factor for death in only one report
(survivor= 0.573±0.068 vs nonsurvivor = 0.697±0.058, p < 0.0001).23

In the analysis
of variance of CTR in relation to death, a clear distinction between groups
(p < 0.0001) was noted after three months, with a 95%CI, being lower or equal
to 0.68 in the survivor group and greater than 0.68 in the nonsurvivor group.
The reviewed literature does not analyze CTR changes over time in relation to
death during patient follow-up.

Chest X-ray was
one of the first ancillary exams used in cardiology and still is considered
useful nowadays because of its ease of use and low cost. The assessment of the
cardiothoracic ratio is extremely simple and useful for the longitudinal follow-up
of pediatric patients with idiopathic dilated cardiomyopathy, serving as an
indicative sign of unfavorable outcome and probable necessity for cardiac transplantation.